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Biomedical subjects

F Oseko

Publications and source records attributed to F Oseko.

At least 19 recordsLinked to original sources

Inhibition of proliferation and differentiation of human B-lymphocytes by a biscoclaurine alkaloid.

A biscoclaurine alkaloid, cepharanthine, is known to be a potent inhibitor of snake venom-induced hemolysis by interaction with the lipid bilayer of the membrane. The drug also interferes with the ion channel intracellularly. In this study, we examined the effect of cepharanthine on human B-cell functions. Small dense B-cells from tonsil samples were isolated using a Percoll density gradient from non-rosetted cells and were used as the target cells. Cepharanthine inhibited the proliferation of the lymphocytes and antibody production of human B-lymphocytes. The inhibitory effect of cepharanthine on the proliferation was caused by the arrest of the late G1 to S phase transition in the cell cycle. However, the mechanism of suppression of antibody formation remains unknown. These results suggest that cepharanthine acts on human B-cells as an immunomodulating agent.

Adjuvants, Immunologic

The suppressive effect of deoxyspergualin on the differentiation of human B lymphocytes maturing into immunoglobulin-producing cells.

Deoxyspergualin, an analog of spergualin, has been known as a novel immunosuppressive agent with strong immunosuppressive activity in in vivo experimental systems. In the present study, we examined the effect of deoxyspergualin (DSG) and methyldeoxyspergualin (MeDSG) on the proliferation and differentiation of human B lymphocytes in vitro. Highly purified B cells from human tonsil samples were isolated by Percoll density gradient from nonrosetted cells and were used as target cells. Both agents had little effect on the proliferative response of resting or activated B lymphocytes. However, they suppressed the immunoglobulin synthesis of B lymphocytes not only in a T cell-dependent, but also in a T cell-independent system. The inhibition of antibody synthesis was manifested in the early stage of B cell differentiation. Both drugs also suppressed Ig secretion, but not proliferation, of an EBV-transformed human B lymphoblastoid cell line. These results indicate that DSG and MeDSG have a selective immunosuppressive effect on the differentiation pathway of B lymphocytes.

Antibody-Producing Cells

The distinct effects of FK506 on the activation, proliferation, and differentiation of human B lymphocytes.

We examined the effect of FK506 on the activation, proliferation and differentiation of human B lymphocytes in vitro. FK506 inhibited the proliferative response of resting B cells induced by Staphylococcus aureus Cowan strain I (SAC) and phorbol myristate acetate (PMA) in a dose-dependent manner. Inhibition of cell proliferation by FK506 was caused by a selective block of G0 to G1 phase transition leading to cell arrest. In addition, the proliferative response of in vivo-activated B cells and lymphokine-driven B cell proliferation were also found to be sensitive to FK506. Interestingly, FK506 did not affect the expression of activation antigens such as CD23, IL-2 receptor (CD25), and transferrin receptor (CD71). Finally, FK506 had little effect on B cell antibody generation in a T cell-independent system. Conversely, FK506 suppressed neither proliferation nor immunoglobulin secretion in a human B lymphoblastoid cell line. These results indicate that FK506 has discrete effects on the different stages of the B cell maturation.

Antibody-Producing Cells

Regulation of lymphocyte blastogenesis and antibody production by soluble factor released by a human B-lymphoblastoid cell line.

Yam 1B, a human B lymphoblastoid cell line, spontaneously produced an immunoregulatory factor, which suppresses blastogenesis and antibody formation by human lymphocytes. The Yam 1B cells, which were derived from the peripheral blood of an adult T-cell leukemia patient, have been established and maintained in our laboratory since 1985. This cell line expressed mature B-cell surface antigens including surface immunoglobulin M (IgM), CD23, and HLA-DR; had cytoplasmic IgM; and secreted small amounts of IgM in the culture supernatants. Yam 1B was positive for Epstein-Barr virus-associated antigen (EBNA) but negative for adult T-cell-associated antigen (ATLA). The serum-free Yam 1B culture supernatants (SN) inhibited the expression of transferrin R, but neither the expression of interleukin 2 (IL-2) R(CD25) nor the production of IL-2 in the lymphocytes stimulated with phytohemagglutin. Yam 1B SN also inhibited DNA synthesis by human T and B lymphocytes and immunoglobulin generation by normal B cells as well as by Epstein-Barr virus-transformed human B lymphoblastoid cell lines. The inhibitory activity of Yam 1B SN was inactivated at 56 degrees C and at pH 10 but was relatively stable at pH 2. It was abrogated by digestion with pronase and was partially stable by digestion with trypsin. Fractions collected from a Sephacryl S-300 gel filtration column (Pharmacia Fine Chemicals, Uppsala, Sweden) were found to have a peak of inhibitory activity of cell proliferation associated with molecules of apparent MWr of 43,000 to 67,000. The inhibitory activity of Yam 1B SN was not blocked by the anti-transforming growth factor beta antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes

The role of CD45RA on human B-cell function: anti-CD45RA antibody (anti-2H4) inhibits the activation of resting B cells and antibody production of activated B cells independently in humans.

Anti-CD45RA antibody defined by anti-2H4 monoclonal antibody has been reported to split CD4+T cells into two distinct subpopulations. CD45RA antigen is present on the surface of virtually more than 95% B lymphocytes in the purified tonsillar B-cell preparations. We examined the role of CD45RA antigen on human B-cell function using this antibody. The addition to anti-2H4 to tonsillar B cells inhibited the proliferative response induced by Staphylococcus aureus Cowan strain I(SAC) in a dose-dependent manner. Kinetic analysis indicated that anti-2H4 exerted its inhibitory effect when added within the first 24 h of culture initiation during a 72-h culture period. Anti-2H4 inhibited the transferrin receptor expression without interfering with the expression of the IL-2 receptor on SAC-stimulated B cells in a short-term culture. Anti-2H4 blocked the progress of SAC-stimulated B cells from the G1 to S phase of the cell cycle. These events suggested that anti-CD45RA MoAb inhibited the proliferative response by directly acting on B cells in the G1 phase. In addition, anti-CD45RA antibody also had a suppressive effect on early phase of B-cell differentiation. This effect appeared to be independent of its suppressive effect on proliferation, because anti-CD45RA did not inhibit the proliferative response of preactivated B cells with lymphokines. These studies suggested that the restricted epitope recognized by anti-2H4 antibody may be directly involved in regulatory function on B cells.

Antibodies, Monoclonal

The role of CD45 in the activation, proliferation and differentiation of human B lymphocytes.

We examined the role of CD45 antigen in human B cell function, using the anti-CD45 antibody, T29/33. The addition of T29/33 to B cells inhibited the proliferative response induced by various polyclonal B cell activators in a dose-dependent manner at concentrations of 0.01 to 10 micrograms/ml. Kinetic analysis indicated that T29/33 exerted its inhibitory effect when added within the first 24 h of culture initiation during a 72-h culture period, but had little effect when added at 48 h. Pre-treatment of high-density B cells with T29/33 antibody for 48 h showed a marked inhibitory effect on the proliferative response of these B cells when they were subsequently stimulated with SAC. Antibody to CD45 appeared to block the G0(G1) to S phase transition in the cell cycle analysis by propidium iodide staining. T29/33 antibody suppressed the RNA and DNA synthesis induced by SAC stimulation in B cells. These data suggested that small resting B cells were sensitive to anti-CD45-induced suppression. T29/33 antibody also suppressed immunoglobulin synthesis in B cells, independently of its suppressive effect on proliferation. These results indicated that CD45 antigen defined by T29/33 is involved in the activation, proliferation, and differentiation signals of human B lymphocytes.

Antigens, CD

Effects of angiotensin I-converting enzyme inhibitor, SQ 14225, in nomal men.

Effects of an orally active angiotensin I-converting enzyme inhibitor, SQ 14225, on the actions of angiotensin I (AI) infused intravenously for 120 to 390 min were studied in 5 normal men. When 20 ng/kg/min of AI infusion was started immediately after a single oral administration of 100 mg of SQ 14225, a significant rise in blood pressure (BP) was observed for the first 15 min, but BP began to fall from 17 min and returned to the pretreatment level at 45 min. This BP level continued at least to 120 min and in one subject to 180 min. In this subject BP began to rise again from 185 min and reached the level of 15 min at 390 min. Plasma AI level increased gradually from 45 min. At 15 min plasma renin activity (PRA) decreased and plasma aldosterone (PA) increased, but then PRA began to increase and PA began to decrease. At 120 min the values of PRA and PA were similar to the pretreatment values. In one subject plasma AI and PRA began to decrease and PA began to increase after 120 or 180 min. On the other hand, in the 5 men sole AI infusion caused a continued BP rise, PRA decrease and PA increase, and sole SQ 14225 administration caused increases in plasma AI and PRA and a decrease in PA but no BP change. From these results it was concluded that complete blockade and partial inhibition of AI conversion by 100 mg of oral SQ 14225 lasted for about 2.5 and 6.5 hr, respectively and that BP rise, PRA suppression and aldosterone stimulation after AI infusion were entirely due to the actions of angiotensin II converted from AI.

Adult

Lack of inhibition of ACTH-induced aldosterone stimulation by des-asp1-,ileu8-angiotensin II in man.

In 5 normal men an intravenous injection of 0.5 mg of synthetic 1-24 ACTH caused a significant increase in plasma aldosterone and a simultaneous intravenous infusion of 600 ng/kg/min of des-asp1-, ileu8-angiotensin II (AIIIA) did not inhibit this increase. Since this dose of AIIIA is known to inhibit an angiotensin II-induced increase in plasma aldosterone in normal men, the present results suggest that the ACTH-induced aldosterone stimulation is mediated by an adrenocortical receptor which is different from angiotensin II receptors.

Adrenocorticotropic Hormone

Bladder carcinoma associated with ectopic production of gonadotropin.

A rare incidence of a primary gonadotropin-producing bladder carcinoma in which gynecomastia appeared in the terminal stage was encountered in a 76-year-old Japanese male. There was a good probability that the symptoms of hormonal activity were due to chorionic gonadotropin (hCG), since its whole molecule, beta- and alpha-subunits were detected by radioimmunoassay in the blood, urine, and the tissue from the malignant neoplasm, and the plasma and urine estrogens were elevated. Recent papers concerning the synthesis of hCG-like material by neoplastic cells are reviewed and the implication of the measurement of beta- and alpha-subunits of hCG in various neoplastic diseases are discussed. Other characteristic profiles of plasma hormonal levels are also discussed in this case.

Aged

Diabetic retinopathy in acromegaly.

A study was made of diabetic retinopathy in acromegaly. 10 of 15 patients with acromegaly had diabetes mellitus, and 3 of the 10 showed diabetic retinopathy. 2 of them had a diabetic family history. 1 patient with a diabetic family history had retinopathy of state IIIa in Scott's classification, and the other 2 showed a few microaneurysms and/or punctate hemorrhages in the macula. Diabetes mellitus and diabetic retinopathy in acromegaly showed no correlation with the duration of acromegaly and diabetes mellitus, age, or growth hormone level. No diabetic cataract was found in the present series. It was concluded that diabetic retinopathy due to secondary diabetes mellitus is usually slight or moderate. Diabetes mellitus with severe retinopathy is probably primary diabetes due to a genetic defect, and secondary diabetes may be different in nature from the primary disease.

Acromegaly

Inhibition of angiotensin III action by DES-ASP1-,ILEU8-angiotensin II in man.

In 5 normal men intravenous infusion of 600 ng/kg/min of des-asp1-ileu8-angiotensin II (AIIIA) inhibited a rise in blood pressure as well as increase in plasma aldosterone caused by an intravenous infusion of 20 or 100 ng/kg/min of des-asp1-angiotensin II (angiotensin III, AIII). This result and our previous study on simultaneous infusions of 600 ng/kg/min of AIIIA and 20 ng/kg/min of angiotensin II (AII) in the same 5 normal men demonstrate that this dose of AIIIA antagonizes AIII and AII on the adrenal cortex as well as peripheral arterioles and that AIIIA has the same degree of inhibitory effect on the aldosterone-stimulating action of AIII and on that of AII in man.

Adult

Biological activity of high dose of des-asp 1-, ileu 8-angiotensin II in man.

The biological activity of high doses of des-asp 1-, ileu 8-angiotensin II (AIIIA) was studied in man. In 5 normal men an intravenous infusion of 600 ng/kg/min of AIIIA for 30 min caused a slight rise in blood pressure, a decrease in plasma renin activity and an increase in plasma aldosterone. This dose inhibited pressor and steroidogenic actions of angiotensin II infused into the same 5 normal men at a rate of 20 ng/kg/min for 30 min. These results are considerably different from our previous report using lower dose (200 ng/kg/min) of AIIIA and indicate that in man AIIIA has both agonist and antagonist activities on the peripheral arterioles as well as on the adrenal cortex.

Aldosterone